T1/CEST双模态MR成像对P-selectin介导的纳米载药体系肿瘤诊疗一体化的研究

Anatomic and functional imaging guided nano-drug delivery system plays an important role in the accurate diagnosis and efficient treatment of cancer. However, how to further optimize the imaging performance, reagent loading efficiency and tumor targeting of nano system urgent to be solved. We previously demonstrated chemical exchange saturation transfer (CEST) MRI could accurately monitor the drug delivery in vivo and sensitively response to the internal tumor microenvironment, such as PH and temperature, etc. On this basis, the study intends to select the mesoporous silica nanoparticles (MSNs) as the nano-carrier; P-selectin as the tumor targeting; and coated with the contrast agents such as gadolinium-coated (Gd) and poly-lysine (PLL) as the dual model of T1 and CEST MRI to rationally design the multi-functional nano-drug delivery system as Gd-PLL @ MSNs. We test the nano-system MR imaging performance and therapeutic efficacy in the triple negative breast cancer and melanoma models. Furthermore, we utilize the PCR, Western blot and immunohistochemistry methods which could provide the different aspects from the mRNA and protein, cell and animal models and other levels, to explore the mechanism and biological signal transduction pathway of the nano-system on tumor, as a result, new scientific evidences for integration of nano-drugs in cancer theranostics may be established.

基于解剖与功能成像引导的纳米载药体系在肿瘤的精确诊断与高效治疗中备受关注。如何进一步优化纳米体系的成像性能、显像剂与药物装载效率和肿瘤靶向性等问题亟待解决。课题组前期发现CEST磁共振成像可以准确示踪药物在体内的传递效率，并监测肿瘤内部微环境（PH值、温度等）的变化过程。本项目拟选取介孔二氧化硅纳米粒（MSNs）为载体，P-selectin为肿瘤靶点，同时包裹钆剂（Gd）、多聚赖氨酸（PLL）构建T1/CEST双模态MR成像的新型纳米载药体系（Gd-PLL@MSNs）；分别应用于三阴性乳腺癌和恶性黑色素瘤模型，重点检测其体内、外的MR成像性能和治疗效果；同时利用PCR、Western blot、免疫组织化学等方法，从mRNA、蛋白、细胞和动物等多个水平深入探讨该多功能纳米体系抑制肿瘤生长的作用机制及相关信号传导通路，为新型肿瘤诊疗一体化纳米药物的研发提供科学依据。

基于解剖与功能成像引导的纳米载药体系在肿瘤的精确诊断与高效治疗中备受关注。如何进一步优化纳米体系的成像性能、显像剂与药物装载效率和肿瘤靶向性等问题亟待解决。课题组前期发现CEST磁共振成像可以准确示踪药物在体内的传递效率，并监测肿瘤内部微环境（PH值、温度等）的变化过程。本项目拟选取介孔二氧化硅纳米粒（MSNs）为载体，P-selectin为肿瘤靶点，同时包裹钆剂（Gd）、多聚赖氨酸（PLL）构建T1/CEST双模态MR成像的新型纳米载药体系（Gd-PLL@MSNs）；分别应用于三阴性乳腺癌和恶性黑色素瘤模型，重点检测其体内、外的MR成像性能和治疗效果；同时利用PCR、Western blot、免疫组织化学等方法，从mRNA、蛋白、细胞和动物等多个水平深入探讨该多功能纳米体系抑制肿瘤生长的作用机制及相关信号传导通路，为新型肿瘤诊疗一体化纳米药物的研发提供科学依据。